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PreprintCC BYbioRxiv

De novo design of allosterically controlled enzymes

  • A. Shida
  • K. Wang
  • H. Choi
  • S. Pellock
  • A. Broerman
  • S. Salike
  • W. Grubbe
  • E. Joyce
  • A. Kang
  • A. K. Bera
  • X. Li
  • A. Pillai
1 more authors
  • D. Baker1
  1. 1Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Ho
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Abstract

The ability of enzymes to sense signals and respond by changing their structure and activity underlies cellular processes from signaling to metabolic control. While there have been recent advances in the de novo design of enzymes and conformationally switching proteins, combining these to achieve allosteric regulation of enzymatic activity in a fully designed system remains an outstanding challenge. Here, we show that denoising diffusion models enable the design of compact de novo enzymes whose activity can be allosterically activated or repressed by designed protein effectors. Our results establish a general route to allosteric control over a wide range of catalytic and other protein functions.

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Cite

BibTeXRIS
BibTeX
@misc{shida2026novo,
  title = {{De novo design of allosterically controlled enzymes}},
  author = {A. Shida and K. Wang and H. Choi and S. Pellock and A. Broerman and S. Salike and W. Grubbe and E. Joyce and A. Kang and A. K. Bera and X. Li and A. Pillai and D. Baker},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.08.750245},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.08.750245v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - De novo design of allosterically controlled enzymes
AU  - A. Shida
AU  - K. Wang
AU  - H. Choi
AU  - S. Pellock
AU  - A. Broerman
AU  - S. Salike
AU  - W. Grubbe
AU  - E. Joyce
AU  - A. Kang
AU  - A. K. Bera
AU  - X. Li
AU  - A. Pillai
AU  - D. Baker
PY  - 2026
DA  - 2026/09/08
PB  - bioRxiv
DO  - 10.64898/2026.09.08.750245
UR  - https://www.biorxiv.org/content/10.64898/2026.09.08.750245v1
AB  - The ability of enzymes to sense signals and respond by changing their structure and activity underlies cellular processes from signaling to metabolic control. While there have been recent advances in the de novo design of enzymes and conformationally switching proteins, combining these to achieve allosteric regulation of enzymatic activity in a fully designed system remains an outstanding challenge. Here, we show that denoising diffusion models enable the design of compact de novo enzymes whose activity can be allosterically activated or repressed by designed protein effectors. Our results establish a general route to allosteric control over a wide range of catalytic and other protein functions.
ER  -